BACKGROUND: Inflammatory bowel disease (IBD) is proposed to result from a dysregulated mucosal immune response to the colonic flora in genetically susceptible individuals. Enterotoxigenic Bacteroides fragilis (ETBF), a molecular subclass of the common human commensal, B. fragilis, has been associated with IBD. This study investigated whether ETBF colonization of mice initiated colitis or modified the clinical course of a colitis agonist, dextran sodium sulfate (DSS). METHODS: Four- and 6-week-old C57BL/6 mice were inoculated with buffer, nontoxigenic B. fragilis (NTBF) strain 9343(pFD340), or ETBF strain 86-5443-2-2 via orogastric tube. A subset of mice received 2% DSS several days pre- or post-inoculation of bacteria. Clinical status was assessed throughout the experiment and severity of colonic inflammation was scored after sacrifice. RESULTS: All mice, including those receiving DSS, were clinically well prior to bacterial inoculation. NTBF and ETBF colonization was similar. Regardless of mouse age or timing of DSS administration, mice who received ETBF+DSS experienced worse colitis reflected by less weight gain, enhanced gross disease, and greater inflammation in their colons (P < 0.05), especially in the cecum. In particular, younger mice had more extensive disease. Mice inoculated only with ETBF also exhibited colitis with more severe inflammation when compared to all other groups (P < 0.05) except the ETBF+DSS group. CONCLUSIONS: ETBF, a colonic commensal, alone stimulates colitis and significantly enhances colonic inflammation in DSS-treated mice. This study suggests that acquisition of ETBF colonization may be a potential factor in initiation and/or exacerbation of colitis.
BACKGROUND:Inflammatory bowel disease (IBD) is proposed to result from a dysregulated mucosal immune response to the colonic flora in genetically susceptible individuals. Enterotoxigenic Bacteroides fragilis (ETBF), a molecular subclass of the common human commensal, B. fragilis, has been associated with IBD. This study investigated whether ETBF colonization of mice initiated colitis or modified the clinical course of a colitis agonist, dextran sodium sulfate (DSS). METHODS: Four- and 6-week-old C57BL/6 mice were inoculated with buffer, nontoxigenic B. fragilis (NTBF) strain 9343(pFD340), or ETBF strain 86-5443-2-2 via orogastric tube. A subset of mice received 2% DSS several days pre- or post-inoculation of bacteria. Clinical status was assessed throughout the experiment and severity of colonic inflammation was scored after sacrifice. RESULTS: All mice, including those receiving DSS, were clinically well prior to bacterial inoculation. NTBF and ETBF colonization was similar. Regardless of mouse age or timing of DSS administration, mice who received ETBF+DSS experienced worse colitis reflected by less weight gain, enhanced gross disease, and greater inflammation in their colons (P < 0.05), especially in the cecum. In particular, younger mice had more extensive disease. Mice inoculated only with ETBF also exhibited colitis with more severe inflammation when compared to all other groups (P < 0.05) except the ETBF+DSS group. CONCLUSIONS:ETBF, a colonic commensal, alone stimulates colitis and significantly enhances colonic inflammation in DSS-treated mice. This study suggests that acquisition of ETBF colonization may be a potential factor in initiation and/or exacerbation of colitis.
Authors: John Penders; Carel Thijs; Cornelis Vink; Foekje F Stelma; Bianca Snijders; Ischa Kummeling; Piet A van den Brandt; Ellen E Stobberingh Journal: Pediatrics Date: 2006-08 Impact factor: 7.124
Authors: Masayuki Fukata; Kathrin S Michelsen; Rajaraman Eri; Lisa S Thomas; Bing Hu; Katie Lukasek; Cynthia C Nast; Juan Lechago; Ruliang Xu; Yoshikazu Naiki; Antoine Soliman; Moshe Arditi; Maria T Abreu Journal: Am J Physiol Gastrointest Liver Physiol Date: 2005-05 Impact factor: 4.052
Authors: Aaron L Hecht; Benjamin W Casterline; Zachary M Earley; Young Ah Goo; David R Goodlett; Juliane Bubeck Wardenburg Journal: EMBO Rep Date: 2016-07-18 Impact factor: 8.807
Authors: Christina E DeStefano Shields; Sara W Van Meerbeke; Franck Housseau; Hao Wang; David L Huso; Robert A Casero; Heather M O'Hagan; Cynthia L Sears Journal: J Infect Dis Date: 2016-02-21 Impact factor: 5.226
Authors: Ki-Jong Rhee; Shaoguang Wu; Xinqun Wu; David L Huso; Baktiar Karim; Augusto A Franco; Shervin Rabizadeh; Jonathan E Golub; Lauren E Mathews; Jai Shin; R Balfour Sartor; Douglas Golenbock; Abdel R Hamad; Christine M Gan; Franck Housseau; Cynthia L Sears Journal: Infect Immun Date: 2009-02-02 Impact factor: 3.441
Authors: Shaoping Wu; Yong-Guo Zhang; Rong Lu; Yinglin Xia; David Zhou; Elaine O Petrof; Erika C Claud; Di Chen; Eugene B Chang; Geert Carmeliet; Jun Sun Journal: Gut Date: 2014-07-30 Impact factor: 23.059